The Toxic Nano-Syringe of Vibrio cholerae.

Type VI secretion systems are used by bacteria to inject toxins into both bacterial competitors and host cells during pathogenesis. A new paper in Nature visualises these nanomachines and shows that they act by the swift contraction of a bacteriophage tail-like tube.

Bacterial type VI secretion systems (T6SS) are used to kill both eukaryotic and prokaryotic cells through the translocation of toxic proteins in a cell-cell contact-dependent process. T6SS encoding clusters of 15-20 genes are found in pathogenicity islands in the genomes of about a quarter of all sequenced gram –ve bacteria. Many T6SS proteins show sequence or structural homology with components of contractile phage tails. For instance, VgrG and Hcp, proteins secreted by T6SS, are structural homologues of a phage needle protein and phage tail tube protein respectively. Likewise, two Vibrio cholerae T6SS components VipA and VipB form tubular structures that resemble the tail sheath of T4 bacteriophage.

To investigate the role of VipA in T6SS, Basler et al. tagged VipA with a green fluorescent protein (GFP) and visualised it’s dynamics in cells. They found that the VipA-GFP fusion proteins were associated with long straight structures in the cell. These were often as long as the width of the cell (0.75-1µm) and varied in number between 0 and 5. By using time-lapse imaging, the researchers found that these putative sheath structures underwent a dynamic pattern of assembly, contraction and disassembly. The extended sheath assembled at a rate of 20-30 s µm-1. Sheaths then contracted to about 50% of their extended length in approximately 5ms. The contracted sheath was then disassembled in 30-60s.

Electron cryotomographic slices of V. cholerae showing Type VI secretion systems in the cytosol. In the left panel the T6SS is in the extended form, in the right it is contracted.


Basler et al. went on to visualise the T6SS sheaths directly using electron cryotomography. This discerned long straight tubular structures that existed in two conformations: A longer and thinner extended structure and a shorter and wider contracted form (see figure). The tubes were connected to the inner membrane by a flared bell-shaped base. Distal to the base in the extended T6SS structures was ‘conical-shaped density’ that crossed the periplasm and protruded through the outer membrane.

The results described in this paper are consistent with a model of T6SS action in which Hcp forms an inner tube within the VipA/VipB sheath. The Hcp tube, tipped with a VgrG ‘needle’ is fired into the target cell membrane by contraction of the T6SS sheath. Thus the energy captured by conformational change of the VipA/VipB polymeric sheath transports the toxic proteins through the cell membrane.

Basler, M., Pilhofer, M., Henderson, G., Jensen, G., & Mekalanos, J. (2012). Type VI secretion requires a dynamic contractile phage tail-like structure Nature, 483 (7388), 182-186 DOI: 10.1038/nature10846

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